Sertraline cytochrome P450 inhibition

Selective serotonin reuptake inhibitors. Currently available selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram. At present, expert opinion does not support the usefulness of these serotonergic compounds in the treatment of core ADHD symptoms (National Institute of Mental Health, 1996). Nevertheless, because of the high rates of comorbidity in ADHD, these compounds are frequently combined with effective anti-ADHD agents (see Combined Pharmacotherapy, below). Since many psychotropics are metabolized by the cytochrome P450 system (Nemeroff et ah, 1996), which in turn can be inhibited by the SSRIs, caution should be exercised when combining agents, such as the TCAs, with SSRIs. 

Liston HL, DeVane CL, Boulton DW, et al. Differential time course of cytochrome P450 2D6 enzyme inhibition by fluoxetine, sertraline, and paroxetine in healthy volunteers. J Clin Psychopharmacol 2002 22 169-173. 

An in vitro investigation found that fluoxetine and fluvoxamine inhibited the metabolism of phenytoin by the cytochrome P450 isoenzyme CYP2C9 in human liver tissue. This would presumably lead to a rise in serum phenytoin levels. In this study, sertraline was a weaker inhibitor of CYP2C9, and was considered less likely to interact with phenytoin.A similar study also suggested that the risk of interaction was greatest for fluoxetine, and less likely with sertraline and paroxetine. Sertraline plasma levels may be reduced because of enzyme induction by phenytoin which would increase its metabolism and clearance from the body. ... 

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6 by which risperidone is metabolised, hence risperidone levels rise. This can lead to extrapyramidal adverse effects and, it has been suggested, the increased prolactin levels and gynaecomastia seen in one patient. Sertraline is thought to have a dose-dependent effects on CYP2D6 inhibition. ... 

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6 thus inhibiting the metabolism of some beta blockers (e.g. propranolol, metoprolol, carvedilol) so that they accumulate, the result being that their effects, such as bradycardia, may be increased. Citalopram and escitalopram may also inhibit CYP2D6. In vitro studies with human liver microsomes found that fluoxetine and paroxetine are potent inhibitors of metoprolol metabolism and fluvoxamine, sertraline and citalopram less potent. However, fluvoxamine also potently inhibits the metabolism of propranolol by CYP1A2. Beta blockers that are not extensively me-... 

Fluvoxamine and nefazodone are inhibitors of the cytochrome P450 isoenzyme CYP3A4, the main isoenzyme by which ciclosporin is metabolised. Concurrent use can therefore lead to increased ciclosporin levels. Fluoxetine may interact similarly. Citalopram and sertraline do not usually signifrcantly inhibit CYP3A4 and would therefore not be expected to interact. 

Tacrolimus is metabolised by the cytochrome P450 isoenzyme CYP3A4, which is inhibited by nefazodone, concurrent use therefore results in increased levels of tacrolimus. Paroxetine and sertraline do not have significant effects on CYP3A4 and are therefore not expected to interact with tacrolimus. 

Fluvoxamine, and to a lesser extent fluoxetine, paroxetine, and sertraline, can inhibit the liver metabolism of the methadone (possibly by the cytochrome P450 isoenzymes CYP3A4," CYP2D6,"- and/or CYP1A2" ) thereby allowing it to accumulate in the body. 

---